We have read the comments raised by Tofts and colleagues and Li and colleagues with great interest. We share their surprise about our finding that—under normal homeostatic conditions—peripheral blood neutrophils have an average life span of 5.4 days, and we welcome their constructive replies to
In mice, recent thymic emigrants (RTEs) make up a large part of the naive T cell pool and have been suggested to be a distinct short-lived pool. In humans, however, the life span and number of RTEs are unknown. Although 2H2O labeling in young mice showed high thymic-dependent daily naive T cell production, long term up- and down-labeling with 2H2O in human adults revealed a low daily production of naive T cells. Using mathematical modeling, we estimated human naive CD4 and CD8 T cell half-lives ...
We describe here a method for measuring DNA replication and, thus, cell proliferation in slow turnover cells that is suitable for use in humans. The technique is based on the incorporation of 2 H 2 O into the deoxyribose (dR) moiety of purine deoxyribonucleotides in dividing cells. For initial validation, rodents were administered 4% 2 H 2 O in drinking water. The proliferation rate of mammary epithelial cells in mice was 2.9% per day and increased 5-fold during pregnancy. Administration of estr...
A method for measuring DNA synthesis and, thus, cell proliferation, in vivo is presented. The technique consists of administering [6,6-2H2]Glc or [U-13C]Glc, isolating genomic DNA, hydrolyzing enzymatically to free deoxyribonucleosides, and derivatizing for GC-MS analysis of dA or dG isotopic enrichments, or both. Comparison of dA or dG to extracellular Glc enrichment (with a correction for intracellular dilution) reveals the fraction of newly synthesized DNA, by application of the precursor-pro...
The effect on human neutrophil NADPH-oxidase activity of the serine protease inhibitor diisopro-pylfluorophosphate (DFP) was investigated. Pretreatment of neutrophils with the protease inhibitor did not affect the release of reactive oxygen species induced by fMLP. However, the intracellular production of reactive oxygen species induced by ionomycin and yeast particles was largely inhibited in DFP treated cells. Production of reactive oxygen species in subcellular fractions was not affected by t...
A method has been developed for measuring neutrophil cellularity in normal human bone marrow, in which the neutrophil-erythroid ratio was determined from marrow sections and marrow normoblasts were estimated by the erythron iron turnover. Neutrophil maturational categories, defined by morphologic criteria, were supported by autoradiographs of marrow flashed-labeled with 3H-thymidine. Correction for multiple counting error was empirically derived by counting serial sections through cells of each ...
The composition of the oral milieu reflects oral health. Saliva provides an environment for multiple microorganisms, and contains soluble factors and immune cells. Neutrophils, which rapidly react on the changes in the microenvironment, are a major immune cell population in saliva and thus may serve as a biomarker for oral pathologies. This review focuses on salivary neutrophils in the oral cavity, their phenotype changes in physiological and pathological conditions, as well as on factors regula...
AbstractIntroduction: Neutrophils are the most abundant inflammatory cells found in the lungs of patients with chronic lung diseases, especially COPD, yet despite this, patients often suffer from r...
Neutrophils are versatile innate effector cells essential for immune defense but also responsible for pathologic inflammation. This dual role complicates therapeutic targeting. However, neither neutrophils themselves nor the pathways they employ as immune effectors are homogeneous, suggesting possibilities for selective intervention. Here we review heterogeneity within the neutrophil population as well as in the pathways mediating neutrophil recruitment to inflamed tissues with a view to outlini...
Neutrophils are crucial for the human innate immunity and constitute the majority of leukocytes in circulation. Thus, blood neutrophil counts serve as a measure for the immune system's functionalit ...
Deuterium is a non-toxic, stable isotope that can safely be administered to humans and mice to study their cellular turnover rates in vivo. It is incorporated into newly synthesized DNA strands during cell division, without interference with the kinetics of cells, and the accumulation and loss of deuterium in the DNA of sorted (sub-)populations of leukocytes can be used to estimate their cellular production rates and lifespans. In the past two decades, this powerful technology has been used to e...
Tissue trauma induces migration and activation of neutrophils through specific mediators. Vacuolated neutrophils in peripheral blood smear of septic patients correlated with mortality. However, scarce data exist with respect to findings in hemorrhagic shock (HS) trauma patients. The aim of this work was to evaluate the number and size of cytoplasmic and nuclear vacuoles in polymorphonuclear neutrophil (PMN) obtained from a peripheral blood smear stained with the May-Grunwald-Giemsa method in tra...
During acute inflammation, 3 neutrophil subsets are found in the blood: neutrophils with a conventional segmented nucleus, neutrophils with a banded nucleus, and T-cell- suppressing CD62Ldim neutrophils with a high number of nuclear lobes. In this study, we compared the in vivo kinetics and proteomes of banded, mature, and hypersegmented neutrophils to determine whether these cell types represent truly different neutrophil subsets or reflect changes induced by lipopolysaccharide (LPS) activation...
Neutropenia is a serious toxic complication of chemotherapeutic treatment. For years, mathematical models have been developed to better predict hematological outcomes during chemotherapy in both the traditional pharmaceutical sciences and mathematical biology disciplines. An increasing number of quantitative systems pharmacology (QSP) models that combine systems approaches, physiology, and pharmacokinetics/pharmacodynamics have been successfully developed. Here, I detail the shift towards QSP ef...
To the editor: In the 5 May 2016 issue of Blood , Silvestre-Roig et al[1][1] explored the phenotypic heterogeneity and the versatility of neutrophils, a heterogeneity established in part by an adaptable neutrophil lifespan. As noted by the authors, the classical understanding of the neutrophil
Last. Derek C. Macallan(St George’s University Hospitals NHS Foundation Trust)H-Index: 42
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Human neutrophils have traditionally been thought to have a short half-life in blood; estimates vary from 4 to 18 hours. This dogma was recently challenged by stable isotope labeling studies with heavy water, which yielded estimates in excess of 3 days. To investigate this disparity, we generated new stable isotope labeling data in healthy adult subjects using both heavy water (n = 4) and deuterium-labeled glucose (n = 9), a compound with more rapid labeling kinetics. To interpret results, we de...